Drug Design and Synthesis Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, 20892, USA.
3 papers in the library · 107 citations · publishing 2017-2022
N-methoxybenzylated derivatives of 2C compounds, specifically 25C-NBOMe and 25I-NBOMe, show higher affinity for 5-HT2A receptors than their parent 2C compounds but are weaker in functional cellular assays. In rats, NBOMes were much more potent at inducing wet dog shakes and back muscle contractions compared to 2C-C and 2C-I. A selective 5-HT2A antagonist reversed these behaviors, confirming receptor involvement. Binding affinities correlated with potencies for back muscle contractions but not wet dog shakes. These findings indicate NBOMes are highly potent 5-HT2A agonists in rats, consistent with reported hallucinogenic effects in humans.
In mice undergoing alcohol abstinence, treatment with ayahuasca blocked the return of alcohol self-administration. The effects depended on activation of the 5-HT2A receptor. The findings suggest that ayahuasca and other 5-HT2A receptor agonists could serve as adjunctive pharmacotherapies for alcohol use disorder.
MDMA and its enantiomers increase affiliative social behaviors and vocalizations in group-housed squirrel monkeys, while methamphetamine has only modest effects. Pretreatment with a 5-HT_2A receptor antagonist or a 5-HT_2C receptor agonist reduces MDMA-induced social behaviors, whereas a 5-HT_1A receptor antagonist does not affect affiliative vocalizations and even increases social contact. These results indicate that the prosocial effects of MDMA depend on 5-HT_2A, but not 5-HT_1A, receptors, aligning with findings in humans and rodents. Understanding these neurochemical mechanisms may aid in developing therapeutics that retain MDMA's social benefits with fewer drawbacks.